Pharmacotherapy for Pregnant Women with Opioid Use Disorder

1 Introduction

This project focuses on Analysis 2 of the Study Protocol, which aims to characterize pregnant individuals with OUD and examine hazards of maternal death and overdose. A poster was presented at Academy Health annual research meeting focusing on analysis on those with OUD and at least one day of MOUD prescription. (Section 7)

2 Study Flow Chart

• Methadone exclusion: n=0 (TennCare OTP coverage began June 2020). Follow-up >1 year exclusion: n=0 (days to event already capped at 365 days).

2.1 Methods

Data Source

• TennCare data
• TN all payer hospitalization database
• Birth and death certificates
• US Census data

Inclusion Criteria

• Women 15-44 years old
• Delivery of an infant >=20 weeks between 2007-2020
• Continuous enrollment in TennCare from 90 pre-delivery through 41 days post partum
• No sickle cell disease or active malignancy
• With and without MOUD receipt initially, but only included those with MOUD for main analysis
• Up to 5-days gap of continuous enrollment

• Exposure: Days of MOUD supply between -90 days prior to delivery and +41 days post-delivery (maximum number of days = 132)
• Covariates also collected during exposure period
• Outcomes: first event of either overdose or death from 42 days post-delivery

Statistical analysis

Descriptive statistics were computed using frequencies (proportions) and medians (IQRs) as appropriate for the overall sample and also stratified by timing of MOUD receipt. Timing of MOUD receipt variable was categorized relative to timing of delivery and has two levels: receipt during one period only either pre- or post-delivery or receipt during both pre- and post-delivery periods. Due to the low number of outcomes, several variables were collapsed into one. These variables are listed below.

• Route of delivery: Cesarean or Vaginal (Vaginal + Forcep + Vacuum)
• Pain conditions: Back pain + dental pain + fibromyalgia + indicator for NSAIDs
• Alcohol use disorder + other substance use
• Benzodiazepine + Anticonvulsant use
• Anxiety + Depression

After calculating the number of days of MOUD receipt, various histograms were plotted to examine differences by method. Then, multivariable Cox Proportional hazards model were used to determine the associations between total days of MOUD receipt as the main exposure and death or overdose as the outcome. For individuals with multiple outcomes, the earliest outcome was used. Outcomes that occurred during the follow-up period were counted if they were captured in the TN all payer database if an individual lost eligibility for TennCare. Average dose per day of MOUD receipt (qty*dose)/(days supply) was also calculated and described in the table. Average days supply and dose from the pre-delivery period that exceeded 90 days was carried over and added to the post-delivery period.

The Cox model was first modeled using linear continuous terms, due to the limited degrees of freedom. However, year of delivery was determined to be non-linear and was modeled using a restricted cubic spline with 3 knots. These models included the following covariates: year of delivery, total day MOUD receipt, age at delivery, gestation weeks, route of delivery, combined pain conditions, alcohol/other substance use, benzodiazepine/anticonvulsant use, anxiety/depression, maternal morbidity (CDC defined). Additional covariates were included initially but were removed due to the small number of outcomes. These include race/ethnicity combined, number of previous pregnancies, schizophrenia/personality disorder, CDC social vulnerability index, and timing of MOUD receipt (one or two periods relative to delivery). Robust standard errors clustered at the individual level were computed.

Additonal notes: few outcomes (<5) prior to 2015

3 Only including data of women with MOUD receipt

3.1 Descriptive Statistics

• There are 9048 pregnancies in 7559 unique individuals

  	N	Overall
  		(N=9359)
  Year of delivery	9359 (100.00)
  Median (interquartile range)		2016 (2014—2018)
  Range		2007—2020
  Age at delivery	9359 (100.00)
  Median (interquartile range)		27 (24—31)
  Range		17—44
  Number of Gestation weeks	9359 (100.00)
  Median (interquartile range)		39 (37—39)
  Range		21—42
  Race	9325 (99.64)
  American Indian or Alaska Native		24/9325 (0.26)
  Asian or Pacific Islander		12/9325 (0.13)
  Black of African American		248/9325 (2.66)
  Other or Unknown		62/9325 (0.66)
  White		8979/9325 (96.29)
  Hispanic : Not Hispanic	9318 (99.56)	9239/9318 (99.15)
  Race/Ethnicity combined	9325 (99.64)
  Hispanic		79/9325 (0.85)
  Non-Hispanic Asian		11/9325 (0.12)
  Non-Hispanic Black		247/9325 (2.65)
  Non-Hispanic Other		62/9325 (0.66)
  Non-Hispanic White		8926/9325 (95.72)
  Route of delivery : Vaginal	9325 (99.64)	6080/9325 (65.20)
  Number of previous pregnancies	9159 (97.86)
  Median (interquartile range)		2 (1—3)
  Range		0—23
  Final outcome	9359 (100.00)
  Death		38/9359 (0.41)
  Overdose		109/9359 (1.16)
  Loss of enrollment		1057/9359 (11.29)
  Censored		8155/9359 (87.14)
  Final outcome (w/o all payer data)	9359 (100.00)
  Death		14/9359 (0.15)
  Overdose		103/9359 (1.10)
  Loss of enrollment		1087/9359 (11.61)
  Censored		8155/9359 (87.14)
  Total days supplied MOUD	9359 (100.00)
  Median (interquartile range)		94 (51—120)
  Range		1—132
  Total days supplied MOUD before delivery	9359 (100.00)
  Median (interquartile range)		73 (31—90)
  Range		0—90
  Total days supplied MOUD after delivery	9359 (100.00)
  Median (interquartile range)		30 (7—42)
  Range		0—42
  Total days supplied MOUD (method 2)	9359 (100.00)
  Median (interquartile range)		98 (51—124)
  Range		1—132
  Total days supplied MOUD before delivery (method 2)	9359 (100.00)
  Median (interquartile range)		73 (31—90)
  Range		0—90
  Total days supplied MOUD after delivery (method 2)	9359 (100.00)
  Median (interquartile range)		30 (12—42)
  Range		0—42
  Total days supplied MOUD (method 3)	9359 (100.00)
  Median (interquartile range)		88 (43—111)
  Range		1—132
  Total days supplied MOUD before delivery (method 3)	9359 (100.00)
  Median (interquartile range)		62 (28—77)
  Range		0—90
  Total days supplied MOUD after delivery (method 3)	9359 (100.00)
  Median (interquartile range)		30 (12—40)
  Range		0—42
  Avg dose pre-delivery (mg)	9282 (99.18)
  Median (interquartile range)		13.97 (8.00—16.00)
  Range		0.00—50.00
  Avg dose post-delivery (mg)	9282 (99.18)
  Median (interquartile range)		9.87 (4.00—16.00)
  Range		0.00—53.57
  Avg dose exposure (mg)	9282 (99.18)
  Median (interquartile range)		14.09 (9.35—16.00)
  Range		0.00—53.57
  Total days buprenorphine before delivery (method 3)	9187 (98.16)
  Median (interquartile range)		62.00 (29.00—78.00)
  Range		0.00—90.00
  Total days buprenorphine after delivery (method 3)	9187 (98.16)
  Median (interquartile range)		30.00 (12.00—40.00)
  Range		0.00—42.00
  Total days supplied buprenorphine	9187 (98.16)
  Median (interquartile range)		89.00 (45.00—112.00)
  Range		1.00—132.00
  Avg dose BUP pre-delivery (mg)	9186 (98.15)
  Median (interquartile range)		13.86 (8.00—16.00)
  Range		0.00—40.00
  Avg dose BUP post-delivery (mg)	9186 (98.15)
  Median (interquartile range)		9.86 (4.00—16.00)
  Range		0.00—42.67
  Avg dose BUP exposure (mg)	9186 (98.15)
  Median (interquartile range)		14.00 (9.15—16.00)
  Range		0.00—42.67
  Type of MOUD	9359 (100.00)
  Both		103/9359 (1.10)
  Buprenorphine only		9084/9359 (97.06)
  Naltrexone only		172/9359 (1.84)
  Combined pain : Yes	9359 (100.00)	7167/9359 (76.58)
  Schizophrenia or personality disorder : Yes	9359 (100.00)	670/9359 (7.16)
  Alcohol or other substance use : Yes	9359 (100.00)	3987/9359 (42.60)
  Benzodiazepine or anticonvulsant use : Yes	9359 (100.00)	1302/9359 (13.91)
  Maternal morbidity : Yes	9359 (100.00)	638/9359 (6.82)
  Anxiety and depression combined : Yes	9359 (100.00)	4061/9359 (43.39)
  Back pain : Yes	9359 (100.00)	3198/9359 (34.17)
  Depression : Yes	9359 (100.00)	3466/9359 (37.03)
  Bipolar disorder : Yes	9359 (100.00)	906/9359 (9.68)
  Other substance use : Yes	9359 (100.00)	3806/9359 (40.67)
  Tobacco use : Yes	9359 (100.00)	6246/9359 (66.74)
  Med NSAIDS : Yes	9359 (100.00)	5697/9359 (60.87)
  Schizophrenia psychotic disorders : Yes	9359 (100.00)	536/9359 (5.73)
  Anxiety : Yes	9359 (100.00)	1753/9359 (18.73)
  Med benzodiazepine use : Yes	9359 (100.00)	890/9359 (9.51)
  Maternal morbidity : Yes	9359 (100.00)	638/9359 (6.82)
  Dental pain : Yes	9359 (100.00)	348/9359 (3.72)
  Alcohol use disorder : Yes	9359 (100.00)	559/9359 (5.97)
  Med anticonvulsant use : Yes	9359 (100.00)	495/9359 (5.29)
  Med muscle relaxant use : Yes	9359 (100.00)	450/9359 (4.81)
  Personality disorder : Yes	9359 (100.00)	247/9359 (2.64)
  Fibromyalgia : Yes	9359 (100.00)	456/9359 (4.87)
  CDC SVI overall percentile ranking of all 4 themes	8723 (93.20)
  Median (interquartile range)		0.58 (0.37—0.78)
  Range		0.00—1.00

  N is the number of non-missing value. ¹Kruskal-Wallis. ²Pearson. ³Wilcoxon.
  
  

3.2 By cases

	N	No outcome	Had outcome	Test Statistic
		(N=9212)	(N=147)
Year of delivery	9359 (100.00)			F1,9357=41.42, P<0.00013
Median (interquartile range)		2016 (2014—2018)	2018 (2016—2019)
Range		2007—2020	2007—2020
Age at delivery	9359 (100.00)			F1,9357=0.54, P=0.46303
Median (interquartile range)		27 (24—31)	27 (25—31)
Range		17—44	19—41
Number of Gestation weeks	9359 (100.00)			F1,9357=7.37, P=0.00663
Median (interquartile range)		39 (37—39)	38 (37—39)
Range		21—42	25—42
Race	9325 (99.64)			Χ2 4=28.07, P<0.00012
American Indian or Alaska Native		23/9178 (0.25)	1/147 (0.68)
Asian or Pacific Islander		12/9178 (0.13)	0/147 (0.00)
Black of African American		243/9178 (2.65)	5/147 (3.40)
Other or Unknown		56/9178 (0.61)	6/147 (4.08)
White		8844/9178 (96.36)	135/147 (91.84)
Hispanic : Not Hispanic	9318 (99.56)	9094/9171 (99.16)	145/147 (98.64)	Χ2 1=0.47, P=0.49432
Race/Ethnicity combined	9325 (99.64)			Χ2 4=27.51, P<0.00012
Hispanic		77/9178 (0.84)	2/147 (1.36)
Non-Hispanic Asian		11/9178 (0.12)	0/147 (0.00)
Non-Hispanic Black		242/9178 (2.64)	5/147 (3.40)
Non-Hispanic Other		56/9178 (0.61)	6/147 (4.08)
Non-Hispanic White		8792/9178 (95.79)	134/147 (91.16)
Route of delivery : Vaginal	9325 (99.64)	5984/9178 (65.20)	96/147 (65.31)	Χ2 1=0.00, P=0.97852
Number of previous pregnancies	9159 (97.86)			F1,9157=1.10, P=0.29413
Median (interquartile range)		2 (1—3)	2 (1—3)
Range		0—23	0—12
Final outcome	9359 (100.00)			Χ2 3=9359.00, P<0.00012
Death		0/9212 (0.00)	38/147 (25.85)
Overdose		0/9212 (0.00)	109/147 (74.15)
Loss of enrollment		1057/9212 (11.47)	0/147 (0.00)
Censored		8155/9212 (88.53)	0/147 (0.00)
Final outcome (w/o all payer data)	9359 (100.00)			Χ2 3=7472.08, P<0.00012
Death		0/9212 (0.00)	14/147 (9.52)
Overdose		0/9212 (0.00)	103/147 (70.07)
Loss of enrollment		1057/9212 (11.47)	30/147 (20.41)
Censored		8155/9212 (88.53)	0/147 (0.00)
Total days supplied MOUD (method 3)	9359 (100.00)			F1,9357=8.92, P=0.00283
Median (interquartile range)		88 (44—112)	73 (30—107)
Range		1—132	2—131
Total days supplied MOUD before delivery (method 3)	9359 (100.00)			F1,9357=4.94, P=0.02633
Median (interquartile range)		62 (29—77)	53 (18—76)
Range		0—90	0—89
Total days supplied MOUD after delivery (method 3)	9359 (100.00)			F1,9357=10.12, P=0.00153
Median (interquartile range)		30 (12—40)	23 (7—36)
Range		0—42	0—42
Avg dose pre-delivery (mg)	9282 (99.18)			F1,9280=0.96, P=0.32633
Median (interquartile range)		13.97 (8.00—16.00)	12.66 (6.38—16.00)
Range		0.00—50.00	0.00—50.00
Avg dose post-delivery (mg)	9282 (99.18)			F1,9280=0.40, P=0.52923
Median (interquartile range)		9.88 (4.00—16.00)	9.13 (0.00—16.00)
Range		0.00—53.57	0.00—31.00
Avg dose exposure (mg)	9282 (99.18)			F1,9280=0.12, P=0.72393
Median (interquartile range)		14.10 (9.39—16.00)	13.83 (8.40—16.00)
Range		0.00—53.57	1.00—50.00
Total days buprenorphine before delivery (method 3)	9187 (98.16)			F1,9185=6.90, P=0.00873
Median (interquartile range)		62.00 (30.00—78.00)	49.00 (17.67—76.00)
Range		0.00—90.00	0.00—89.00
Total days buprenorphine after delivery (method 3)	9187 (98.16)			F1,9185=13.82, P=0.00023
Median (interquartile range)		30.00 (12.00—40.00)	22.00 (5.00—36.00)
Range		0.00—42.00	0.00—42.00
Total days supplied buprenorphine	9187 (98.16)			F1,9185=12.02, P=0.00053
Median (interquartile range)		89.00 (45.00—112.00)	71.00 (28.00—105.67)
Range		1.00—132.00	2.00—131.00
Avg dose BUP pre-delivery (mg)	9186 (98.15)			F1,9184=2.08, P=0.14933
Median (interquartile range)		13.87 (8.00—16.00)	12.44 (6.14—16.00)
Range		0.00—40.00	0.00—24.24
Avg dose BUP post-delivery (mg)	9186 (98.15)			F1,9184=0.13, P=0.71753
Median (interquartile range)		9.87 (4.00—16.00)	9.18 (0.00—16.00)
Range		0.00—42.67	0.00—31.00
Avg dose BUP exposure (mg)	9186 (98.15)			F1,9184=0.00, P=0.97753
Median (interquartile range)		14.00 (9.18—16.00)	13.36 (8.38—16.00)
Range		0.00—42.67	1.00—31.00
Combined pain : Yes	9359 (100.00)	7062/9212 (76.66)	105/147 (71.43)	Χ2 1=2.21, P=0.13722
Schizophrenia or personality disorder : Yes	9359 (100.00)	649/9212 (7.05)	21/147 (14.29)	Χ2 1=11.41, P=0.00072
Alcohol or other substance use : Yes	9359 (100.00)	3915/9212 (42.50)	72/147 (48.98)	Χ2 1=2.49, P=0.11492
Benzodiazepine or anticonvulsant use : Yes	9359 (100.00)	1274/9212 (13.83)	28/147 (19.05)	Χ2 1=3.29, P=0.06972
Maternal morbidity : Yes	9359 (100.00)	628/9212 (6.82)	10/147 (6.80)	Χ2 1=0.00, P=0.99452
Anxiety and depression combined : Yes	9359 (100.00)	3968/9212 (43.07)	93/147 (63.27)	Χ2 1=24.01, P<0.00012
Back pain : Yes	9359 (100.00)	3163/9212 (34.34)	35/147 (23.81)	Χ2 1=7.13, P=0.00762
Depression : Yes	9359 (100.00)	3380/9212 (36.69)	86/147 (58.50)	Χ2 1=29.52, P<0.00012
Bipolar disorder : Yes	9359 (100.00)	875/9212 (9.50)	31/147 (21.09)	Χ2 1=22.23, P<0.00012
Other substance use : Yes	9359 (100.00)	3736/9212 (40.56)	70/147 (47.62)	Χ2 1=2.99, P=0.08372
Tobacco use : Yes	9359 (100.00)	6139/9212 (66.64)	107/147 (72.79)	Χ2 1=2.46, P=0.11652
Med NSAIDS : Yes	9359 (100.00)	5611/9212 (60.91)	86/147 (58.50)	Χ2 1=0.35, P=0.55312
Schizophrenia psychotic disorders : Yes	9359 (100.00)	517/9212 (5.61)	19/147 (12.93)	Χ2 1=14.33, P=0.00022
Anxiety : Yes	9359 (100.00)	1706/9212 (18.52)	47/147 (31.97)	Χ2 1=17.20, P<0.00012
Med benzodiazepine use : Yes	9359 (100.00)	875/9212 (9.50)	15/147 (10.20)	Χ2 1=0.08, P=0.77232
Maternal morbidity : Yes	9359 (100.00)	628/9212 (6.82)	10/147 (6.80)	Χ2 1=0.00, P=0.99452
Dental pain : Yes	9359 (100.00)	341/9212 (3.70)	7/147 (4.76)	Χ2 1=0.45, P=0.50032
Alcohol use disorder : Yes	9359 (100.00)	535/9212 (5.81)	24/147 (16.33)	Χ2 1=28.51, P<0.00012
Med anticonvulsant use : Yes	9359 (100.00)	479/9212 (5.20)	16/147 (10.88)	Χ2 1=9.33, P=0.00222
Med muscle relaxant use : Yes	9359 (100.00)	441/9212 (4.79)	9/147 (6.12)	Χ2 1=0.56, P=0.45282
Personality disorder : Yes	9359 (100.00)	240/9212 (2.61)	7/147 (4.76)	Χ2 1=2.62, P=0.10562
Fibromyalgia : Yes	9359 (100.00)	449/9212 (4.87)	7/147 (4.76)	Χ2 1=0.00, P=0.95002
CDC SVI overall percentile ranking of all 4 themes	8723 (93.20)			F1,8721=0.58, P=0.44633
Median (interquartile range)		0.58 (0.37—0.78)	0.54 (0.33—0.81)
Range		0.00—1.00	0.00—1.00

N is the number of non-missing value. ¹Kruskal-Wallis. ²Pearson. ³Wilcoxon.

3.3 MOUD information

	N	All
		(N=9359)
MOUD pre-delivery (method 1)	9359 (100.00)
No MOUD		847/9359 (9.05)
MOUD		8512/9359 (90.95)
MOUD pre-delivery (method 2)	9359 (100.00)
No MOUD		847/9359 (9.05)
MOUD		8512/9359 (90.95)
MOUD pre-delivery (method 3)	9359 (100.00)
No MOUD		854/9359 (9.12)
MOUD		8505/9359 (90.88)
MOUD post-delivery (method 1)	9359 (100.00)
No MOUD		1946/9359 (20.79)
MOUD		7413/9359 (79.21)
MOUD post-delivery (method 2)	9359 (100.00)
No MOUD		1715/9359 (18.32)
MOUD		7644/9359 (81.68)
MOUD post-delivery (method 3)	9359 (100.00)
No MOUD		1218/9359 (13.01)
MOUD		8141/9359 (86.99)
MOUD pre and post (method 1)	9359 (100.00)
No MOUD		0/9359 (0.00)
Both pre and post		6566/9359 (70.16)
Either pre or post		2793/9359 (29.84)
MOUD pre and post (method 2)	9359 (100.00)
No MOUD		0/9359 (0.00)
Both pre and post		6797/9359 (72.63)
Either pre or post		2562/9359 (27.37)
MOUD pre and post (method 3)	9359 (100.00)
No MOUD		0/9359 (0.00)
Both pre and post		7287/9359 (77.86)
Either pre or post		2072/9359 (22.14)

N is the number of non-missing value. ¹Kruskal-Wallis. ²Pearson. ³Wilcoxon.

3.4 Characteristics based on MOUD timing (method 3)

3.4.1 Two categories

	N	Both pre and post	Either pre or post	Test Statistic
		(N=7287)	(N=2072)
Year of delivery	9359 (100.00)			F1,9357=4.08, P=0.04343
Median (interquartile range)		2016 (2014—2018)	2016 (2014—2018)
Range		2007—2020	2007—2020
Year of delivery as categorical	9359 (100.00)			Χ2 13=54.13, P<0.00012
2007		37/7287 (0.51)	16/2072 (0.77)
2008		80/7287 (1.10)	44/2072 (2.12)
2009		135/7287 (1.85)	46/2072 (2.22)
2010		217/7287 (2.98)	68/2072 (3.28)
2011		265/7287 (3.64)	75/2072 (3.62)
2012		364/7287 (5.00)	77/2072 (3.72)
2013		577/7287 (7.92)	131/2072 (6.32)
2014		787/7287 (10.80)	176/2072 (8.49)
2015		962/7287 (13.20)	241/2072 (11.63)
2016		874/7287 (11.99)	260/2072 (12.55)
2017		728/7287 (9.99)	254/2072 (12.26)
2018		711/7287 (9.76)	237/2072 (11.44)
2019		734/7287 (10.07)	230/2072 (11.10)
2020		816/7287 (11.20)	217/2072 (10.47)
Age at delivery	9359 (100.00)			F1,9357=6.22, P=0.01263
Median (interquartile range)		27 (24—31)	27 (24—30)
Range		17—44	17—44
Number of Gestation weeks	9359 (100.00)			F1,9357=9.81, P=0.00173
Median (interquartile range)		39 (37—39)	39 (37—39)
Range		21—42	23—42
Race	9325 (99.64)			Χ2 4=7.51, P=0.11132
American Indian or Alaska Native		17/7261 (0.23)	7/2064 (0.34)
Asian or Pacific Islander		10/7261 (0.14)	2/2064 (0.10)
Black of African American		179/7261 (2.47)	69/2064 (3.34)
Other or Unknown		44/7261 (0.61)	18/2064 (0.87)
White		7011/7261 (96.56)	1968/2064 (95.35)
Hispanic : Not Hispanic	9318 (99.56)	7194/7258 (99.12)	2045/2060 (99.27)	Χ2 1=0.45, P=0.50212
Race/Ethnicity combined	9325 (99.64)			Χ2 4=11.36, P=0.02282
Hispanic		64/7261 (0.88)	15/2064 (0.73)
Non-Hispanic Asian		9/7261 (0.12)	2/2064 (0.10)
Non-Hispanic Black		179/7261 (2.47)	68/2064 (3.29)
Non-Hispanic Other		40/7261 (0.55)	22/2064 (1.07)
Non-Hispanic White		6969/7261 (95.98)	1957/2064 (94.82)
Route of delivery : Vaginal	9325 (99.64)	4688/7261 (64.56)	1392/2064 (67.44)	Χ2 1=5.87, P=0.01542
Number of previous pregnancies	9159 (97.86)			F1,9157=0.03, P=0.87343
Median (interquartile range)		2 (1—3)	2 (1—3)
Range		0—23	0—23
Final outcome	9359 (100.00)			Χ2 3=27.30, P<0.00012
Death		30/7287 (0.41)	8/2072 (0.39)
Overdose		72/7287 (0.99)	37/2072 (1.79)
Loss of enrollment		770/7287 (10.57)	287/2072 (13.85)
Censored		6415/7287 (88.03)	1740/2072 (83.98)
Final outcome 3 levels	9359 (100.00)			Χ2 2=8.94, P=0.01152
Death		30/7287 (0.41)	8/2072 (0.39)
Overdose		72/7287 (0.99)	37/2072 (1.79)
Censored		7185/7287 (98.60)	2027/2072 (97.83)
Total days supplied MOUD	9359 (100.00)			F1,9357=7091.96, P<0.00013
Median (interquartile range)		108 (85—122)	28 (14—42)
Range		2—132	1—90
Total days supplied MOUD before delivery	9359 (100.00)			F1,9357=5339.94, P<0.00013
Median (interquartile range)		84 (60—90)	10 (0—33)
Range		1—90	0—90
Total days supplied MOUD after delivery	9359 (100.00)			F1,9357=2392.80, P<0.00013
Median (interquartile range)		30 (21—42)	0 (0—21)
Range		0—42	0—42
Total days supplied MOUD (method 2)	9359 (100.00)			F1,9357=6945.16, P<0.00013
Median (interquartile range)		112 (85—129)	28 (14—42)
Range		2—132	1—132
Total days supplied MOUD before delivery (method 2)	9359 (100.00)			F1,9357=5339.94, P<0.00013
Median (interquartile range)		84 (60—90)	10 (0—33)
Range		1—90	0—90
Total days supplied MOUD after delivery (method 2)	9359 (100.00)			F1,9357=2900.08, P<0.00013
Median (interquartile range)		35 (24—42)	0 (0—21)
Range		0—42	0—42
Total days supplied MOUD (method 3)	9359 (100.00)			F1,9357=7143.32, P<0.00013
Median (interquartile range)		100 (76—116)	21 (10—33)
Range		2—132	1—89
Total days supplied MOUD before delivery (method 3)	9359 (100.00)			F1,9357=4450.56, P<0.00013
Median (interquartile range)		69 (49—80)	9 (0—30)
Range		1—90	0—89
Total days supplied MOUD after delivery (method 3)	9359 (100.00)			F1,9357=5787.87, P<0.00013
Median (interquartile range)		35 (23—41)	0 (0—11)
Range		1—42	0—41
Avg dose pre-delivery (mg)	9282 (99.18)			F1,9280=1053.26, P<0.00013
Median (interquartile range)		14.87 (9.73—16.00)	6.95 (0.00—15.75)
Range		0.25—50.00	0.00—50.00
Avg dose post-delivery (mg)	9282 (99.18)			F1,9280=1080.50, P<0.00013
Median (interquartile range)		12.00 (8.00—16.00)	0.00 (0.00—12.27)
Range		0.00—50.00	0.00—53.57
Avg dose exposure (mg)	9282 (99.18)			F1,9280=4.55, P=0.03303
Median (interquartile range)		14.00 (9.82—16.00)	14.81 (8.00—16.00)
Range		0.25—50.00	0.00—53.57
Total days buprenorphine before delivery (method 3)	9187 (98.16)			F1,9185=4050.62, P<0.00013
Median (interquartile range)		69.00 (49.00—80.00)	12.00 (0.00—32.00)
Range		0.00—90.00	0.00—89.00
Total days buprenorphine after delivery (method 3)	9187 (98.16)			F1,9185=5433.57, P<0.00013
Median (interquartile range)		35.00 (23.00—41.00)	0.00 (0.00—9.00)
Range		0.00—42.00	0.00—41.00
Total days supplied buprenorphine	9187 (98.16)			F1,9185=6525.03, P<0.00013
Median (interquartile range)		100.00 (76.00—116.00)	21.00 (10.00—34.00)
Range		2.00—132.00	1.00—89.00
Avg dose BUP pre-delivery (mg)	9186 (98.15)			F1,9184=1053.07, P<0.00013
Median (interquartile range)		14.77 (9.54—16.00)	7.00 (0.00—15.63)
Range		0.00—40.00	0.00—32.00
Avg dose BUP post-delivery (mg)	9186 (98.15)			F1,9184=1143.86, P<0.00013
Median (interquartile range)		12.00 (8.00—16.00)	0.00 (0.00—12.00)
Range		0.00—33.24	0.00—42.67
Avg dose BUP exposure (mg)	9186 (98.15)			F1,9184=1.28, P=0.25873
Median (interquartile range)		13.95 (9.71—16.00)	14.48 (8.00—16.00)
Range		0.25—34.47	0.00—42.67
Combined pain : Yes	9359 (100.00)	5600/7287 (76.85)	1567/2072 (75.63)	Χ2 1=1.34, P=0.24662
Schizophrenia or personality disorder : Yes	9359 (100.00)	495/7287 (6.79)	175/2072 (8.45)	Χ2 1=6.63, P=0.01002
Alcohol or other substance use : Yes	9359 (100.00)	3072/7287 (42.16)	915/2072 (44.16)	Χ2 1=2.65, P=0.10382
Benzodiazepine or anticonvulsant use : Yes	9359 (100.00)	1033/7287 (14.18)	269/2072 (12.98)	Χ2 1=1.92, P=0.16612
Maternal morbidity : Yes	9359 (100.00)	490/7287 (6.72)	148/2072 (7.14)	Χ2 1=0.44, P=0.50482
Anxiety and depression combined : Yes	9359 (100.00)	3160/7287 (43.36)	901/2072 (43.48)	Χ2 1=0.01, P=0.92272
Back pain : Yes	9359 (100.00)	2514/7287 (34.50)	684/2072 (33.01)	Χ2 1=1.59, P=0.20762
Depression : Yes	9359 (100.00)	2688/7287 (36.89)	778/2072 (37.55)	Χ2 1=0.30, P=0.58272
Bipolar disorder : Yes	9359 (100.00)	709/7287 (9.73)	197/2072 (9.51)	Χ2 1=0.09, P=0.76312
Other substance use : Yes	9359 (100.00)	2919/7287 (40.06)	887/2072 (42.81)	Χ2 1=5.06, P=0.02452
Tobacco use : Yes	9359 (100.00)	4859/7287 (66.68)	1387/2072 (66.94)	Χ2 1=0.05, P=0.82472
Med NSAIDS : Yes	9359 (100.00)	4453/7287 (61.11)	1244/2072 (60.04)	Χ2 1=0.78, P=0.37842
Schizophrenia psychotic disorders : Yes	9359 (100.00)	400/7287 (5.49)	136/2072 (6.56)	Χ2 1=3.45, P=0.06332
Anxiety : Yes	9359 (100.00)	1357/7287 (18.62)	396/2072 (19.11)	Χ2 1=0.25, P=0.61412
Med benzodiazepine use : Yes	9359 (100.00)	697/7287 (9.56)	193/2072 (9.31)	Χ2 1=0.12, P=0.73182
Maternal morbidity : Yes	9359 (100.00)	490/7287 (6.72)	148/2072 (7.14)	Χ2 1=0.44, P=0.50482
Dental pain : Yes	9359 (100.00)	257/7287 (3.53)	91/2072 (4.39)	Χ2 1=3.37, P=0.06632
Alcohol use disorder : Yes	9359 (100.00)	419/7287 (5.75)	140/2072 (6.76)	Χ2 1=2.91, P=0.08792
Med anticonvulsant use : Yes	9359 (100.00)	404/7287 (5.54)	91/2072 (4.39)	Χ2 1=4.28, P=0.03872
Med muscle relaxant use : Yes	9359 (100.00)	313/7287 (4.30)	137/2072 (6.61)	Χ2 1=18.92, P<0.00012
Personality disorder : Yes	9359 (100.00)	174/7287 (2.39)	73/2072 (3.52)	Χ2 1=8.09, P=0.00442
Fibromyalgia : Yes	9359 (100.00)	349/7287 (4.79)	107/2072 (5.16)	Χ2 1=0.49, P=0.48452
CDC SVI overall percentile ranking of all 4 themes	8723 (93.20)			F1,8721=4.39, P=0.03613
Median (interquartile range)		0.57 (0.37—0.78)	0.60 (0.38—0.79)
Range		0.00—1.00	0.00—1.00

N is the number of non-missing value. ¹Kruskal-Wallis. ²Pearson. ³Wilcoxon.

3.4.2 Three categories

	N	Only pre	Only post	Both pre and post	Test Statistic
		(N=1218)	(N=854)	(N=7287)
Year of delivery	9359 (100.00)				F2,9356=7.83, P=0.00041
Median (interquartile range)		2016 (2014—2018)	2016 (2013—2019)	2016 (2014—2018)
Range		2007—2020	2007—2020	2007—2020
Year of delivery as categorical	9359 (100.00)				Χ2 26=214.59, P<0.00012
2007		3/1218 (0.25)	13/854 (1.52)	37/7287 (0.51)
2008		10/1218 (0.82)	34/854 (3.98)	80/7287 (1.10)
2009		16/1218 (1.31)	30/854 (3.51)	135/7287 (1.85)
2010		19/1218 (1.56)	49/854 (5.74)	217/7287 (2.98)
2011		40/1218 (3.28)	35/854 (4.10)	265/7287 (3.64)
2012		46/1218 (3.78)	31/854 (3.63)	364/7287 (5.00)
2013		69/1218 (5.67)	62/854 (7.26)	577/7287 (7.92)
2014		105/1218 (8.62)	71/854 (8.31)	787/7287 (10.80)
2015		161/1218 (13.22)	80/854 (9.37)	962/7287 (13.20)
2016		186/1218 (15.27)	74/854 (8.67)	874/7287 (11.99)
2017		166/1218 (13.63)	88/854 (10.30)	728/7287 (9.99)
2018		170/1218 (13.96)	67/854 (7.85)	711/7287 (9.76)
2019		129/1218 (10.59)	101/854 (11.83)	734/7287 (10.07)
2020		98/1218 (8.05)	119/854 (13.93)	816/7287 (11.20)
Age at delivery	9359 (100.00)				F2,9356=3.38, P=0.03421
Median (interquartile range)		27 (24—30)	27 (24—31)	27 (24—31)
Range		17—43	17—44	17—44
Number of Gestation weeks	9359 (100.00)				F2,9356=7.71, P=0.00051
Median (interquartile range)		39 (37—39)	38 (37—39)	39 (37—39)
Range		24—42	23—42	21—42
Race	9325 (99.64)				Χ2 8=10.23, P=0.24922
American Indian or Alaska Native		4/1215 (0.33)	3/849 (0.35)	17/7261 (0.23)
Asian or Pacific Islander		1/1215 (0.08)	1/849 (0.12)	10/7261 (0.14)
Black of African American		44/1215 (3.62)	25/849 (2.94)	179/7261 (2.47)
Other or Unknown		13/1215 (1.07)	5/849 (0.59)	44/7261 (0.61)
White		1153/1215 (94.90)	815/849 (96.00)	7011/7261 (96.56)
Hispanic : Not Hispanic	9318 (99.56)	1202/1212 (99.17)	843/848 (99.41)	7194/7258 (99.12)	Χ2 2=0.78, P=0.67722
Race/Ethnicity combined	9325 (99.64)				Χ2 8=13.75, P=0.08862
Hispanic		10/1215 (0.82)	5/849 (0.59)	64/7261 (0.88)
Non-Hispanic Asian		1/1215 (0.08)	1/849 (0.12)	9/7261 (0.12)
Non-Hispanic Black		43/1215 (3.54)	25/849 (2.94)	179/7261 (2.47)
Non-Hispanic Other		15/1215 (1.23)	7/849 (0.82)	40/7261 (0.55)
Non-Hispanic White		1146/1215 (94.32)	811/849 (95.52)	6969/7261 (95.98)
Route of delivery : Vaginal	9325 (99.64)	829/1215 (68.23)	563/849 (66.31)	4688/7261 (64.56)	Χ2 2=6.68, P=0.03552
Number of previous pregnancies	9159 (97.86)				F2,9156=0.01, P=0.98511
Median (interquartile range)		2 (1—3)	2 (1—3)	2 (1—3)
Range		0—19	0—23	0—23
Final outcome	9359 (100.00)				Χ2 6=33.81, P<0.00012
Death		3/1218 (0.25)	5/854 (0.59)	30/7287 (0.41)
Overdose		20/1218 (1.64)	17/854 (1.99)	72/7287 (0.99)
Loss of enrollment		154/1218 (12.64)	133/854 (15.57)	770/7287 (10.57)
Censored		1041/1218 (85.47)	699/854 (81.85)	6415/7287 (88.03)
Final outcome 3 levels	9359 (100.00)				Χ2 4=10.91, P=0.02762
Death		3/1218 (0.25)	5/854 (0.59)	30/7287 (0.41)
Overdose		20/1218 (1.64)	17/854 (1.99)	72/7287 (0.99)
Censored		1195/1218 (98.11)	832/854 (97.42)	7185/7287 (98.60)
Total days supplied MOUD	9359 (100.00)				F2,9356=3572.35, P<0.00011
Median (interquartile range)		30 (14—55)	28 (14—32)	108 (85—122)
Range		1—90	1—70	2—132
Total days supplied MOUD before delivery	9359 (100.00)				F2,9356=3078.44, P<0.00011
Median (interquartile range)		30 (14—55)	0 (0—0)	84 (60—90)
Range		1—90	0—28	1—90
Total days supplied MOUD after delivery	9359 (100.00)				F2,9356=1988.85, P<0.00011
Median (interquartile range)		0 (0—0)	28 (14—32)	30 (21—42)
Range		0—0	1—42	0—42
Total days supplied MOUD (method 2)	9359 (100.00)				F2,9356=3503.49, P<0.00011
Median (interquartile range)		30 (14—55)	28 (14—32)	112 (85—129)
Range		1—132	1—70	2—132
Total days supplied MOUD before delivery (method 2)	9359 (100.00)				F2,9356=3078.44, P<0.00011
Median (interquartile range)		30 (14—55)	0 (0—0)	84 (60—90)
Range		1—90	0—28	1—90
Total days supplied MOUD after delivery (method 2)	9359 (100.00)				F2,9356=2176.25, P<0.00011
Median (interquartile range)		0 (0—0)	28 (14—32)	35 (24—42)
Range		0—42	1—42	0—42
Total days supplied MOUD (method 3)	9359 (100.00)				F2,9356=3649.63, P<0.00011
Median (interquartile range)		30 (14—47)	14 (7—24)	100 (76—116)
Range		1—89	1—41	2—132
Total days supplied MOUD before delivery (method 3)	9359 (100.00)				F2,9356=2662.51, P<0.00011
Median (interquartile range)		30 (14—47)	0 (0—0)	69 (49—80)
Range		1—89	0—0	1—90
Total days supplied MOUD after delivery (method 3)	9359 (100.00)				F2,9356=3413.89, P<0.00011
Median (interquartile range)		0 (0—0)	14 (7—24)	35 (23—41)
Range		0—0	1—41	1—42
Avg dose pre-delivery (mg)	9282 (99.18)				F2,9279=1462.30, P<0.00011
Median (interquartile range)		13.71 (8.00—16.00)	0.00 (0.00—0.00)	14.87 (9.73—16.00)
Range		0.00—50.00	0.00—0.00	0.25—50.00
Avg dose post-delivery (mg)	9282 (99.18)				F2,9279=1981.82, P<0.00011
Median (interquartile range)		0.00 (0.00—0.00)	16.00 (8.40—16.00)	12.00 (8.00—16.00)
Range		0.00—0.00	0.00—53.57	0.00—50.00
Avg dose exposure (mg)	9282 (99.18)				F2,9279=21.39, P<0.00011
Median (interquartile range)		13.71 (8.00—16.00)	16.00 (8.40—16.00)	14.00 (9.82—16.00)
Range		0.00—50.00	0.00—53.57	0.25—50.00
Total days buprenorphine before delivery (method 3)	9187 (98.16)				F2,9184=2397.26, P<0.00011
Median (interquartile range)		30.00 (14.00—47.00)	0.00 (0.00—0.00)	69.00 (49.00—80.00)
Range		1.00—89.00	0.00—0.00	0.00—90.00
Total days buprenorphine after delivery (method 3)	9187 (98.16)				F2,9184=3179.55, P<0.00011
Median (interquartile range)		0.00 (0.00—0.00)	14.00 (7.00—24.00)	35.00 (23.00—41.00)
Range		0.00—0.00	1.00—41.00	0.00—42.00
Total days supplied buprenorphine	9187 (98.16)				F2,9184=3325.60, P<0.00011
Median (interquartile range)		30.00 (14.00—47.00)	14.00 (7.00—24.00)	100.00 (76.00—116.00)
Range		1.00—89.00	1.00—41.00	2.00—132.00
Avg dose BUP pre-delivery (mg)	9186 (98.15)				F2,9183=1415.08, P<0.00011
Median (interquartile range)		13.38 (8.00—16.00)	0.00 (0.00—0.00)	14.77 (9.54—16.00)
Range		0.00—32.00	0.00—0.00	0.00—40.00
Avg dose BUP post-delivery (mg)	9186 (98.15)				F2,9183=1936.83, P<0.00011
Median (interquartile range)		0.00 (0.00—0.00)	16.00 (8.40—16.00)	12.00 (8.00—16.00)
Range		0.00—0.00	0.00—42.67	0.00—33.24
Avg dose BUP exposure (mg)	9186 (98.15)				F2,9183=17.50, P<0.00011
Median (interquartile range)		13.38 (8.00—16.00)	16.00 (8.40—16.00)	13.95 (9.71—16.00)
Range		0.00—32.00	0.00—42.67	0.25—34.47
Combined pain : Yes	9359 (100.00)	934/1218 (76.68)	633/854 (74.12)	5600/7287 (76.85)	Χ2 2=3.18, P=0.20402
Schizophrenia or personality disorder : Yes	9359 (100.00)	97/1218 (7.96)	78/854 (9.13)	495/7287 (6.79)	Χ2 2=7.67, P=0.02162
Alcohol or other substance use : Yes	9359 (100.00)	544/1218 (44.66)	371/854 (43.44)	3072/7287 (42.16)	Χ2 2=2.95, P=0.22852
Benzodiazepine or anticonvulsant use : Yes	9359 (100.00)	160/1218 (13.14)	109/854 (12.76)	1033/7287 (14.18)	Χ2 2=1.98, P=0.37222
Maternal morbidity : Yes	9359 (100.00)	87/1218 (7.14)	61/854 (7.14)	490/7287 (6.72)	Χ2 2=0.44, P=0.80052
Anxiety and depression combined : Yes	9359 (100.00)	500/1218 (41.05)	401/854 (46.96)	3160/7287 (43.36)	Χ2 2=7.13, P=0.02822
Back pain : Yes	9359 (100.00)	414/1218 (33.99)	270/854 (31.62)	2514/7287 (34.50)	Χ2 2=2.85, P=0.24092
Depression : Yes	9359 (100.00)	424/1218 (34.81)	354/854 (41.45)	2688/7287 (36.89)	Χ2 2=9.80, P=0.00752
Bipolar disorder : Yes	9359 (100.00)	131/1218 (10.76)	66/854 (7.73)	709/7287 (9.73)	Χ2 2=5.35, P=0.06882
Other substance use : Yes	9359 (100.00)	531/1218 (43.60)	356/854 (41.69)	2919/7287 (40.06)	Χ2 2=5.82, P=0.05452
Tobacco use : Yes	9359 (100.00)	852/1218 (69.95)	535/854 (62.65)	4859/7287 (66.68)	Χ2 2=12.11, P=0.00232
Med NSAIDS : Yes	9359 (100.00)	737/1218 (60.51)	507/854 (59.37)	4453/7287 (61.11)	Χ2 2=1.05, P=0.59142
Schizophrenia psychotic disorders : Yes	9359 (100.00)	77/1218 (6.32)	59/854 (6.91)	400/7287 (5.49)	Χ2 2=3.77, P=0.15182
Anxiety : Yes	9359 (100.00)	241/1218 (19.79)	155/854 (18.15)	1357/7287 (18.62)	Χ2 2=1.14, P=0.56622
Med benzodiazepine use : Yes	9359 (100.00)	118/1218 (9.69)	75/854 (8.78)	697/7287 (9.56)	Χ2 2=0.60, P=0.74232
Maternal morbidity : Yes	9359 (100.00)	87/1218 (7.14)	61/854 (7.14)	490/7287 (6.72)	Χ2 2=0.44, P=0.80052
Dental pain : Yes	9359 (100.00)	54/1218 (4.43)	37/854 (4.33)	257/7287 (3.53)	Χ2 2=3.39, P=0.18392
Alcohol use disorder : Yes	9359 (100.00)	72/1218 (5.91)	68/854 (7.96)	419/7287 (5.75)	Χ2 2=6.67, P=0.03562
Med anticonvulsant use : Yes	9359 (100.00)	54/1218 (4.43)	37/854 (4.33)	404/7287 (5.54)	Χ2 2=4.29, P=0.11732
Med muscle relaxant use : Yes	9359 (100.00)	72/1218 (5.91)	65/854 (7.61)	313/7287 (4.30)	Χ2 2=22.09, P<0.00012
Personality disorder : Yes	9359 (100.00)	38/1218 (3.12)	35/854 (4.10)	174/7287 (2.39)	Χ2 2=9.96, P=0.00692
Fibromyalgia : Yes	9359 (100.00)	63/1218 (5.17)	44/854 (5.15)	349/7287 (4.79)	Χ2 2=0.49, P=0.78302
CDC SVI overall percentile ranking of all 4 themes	8723 (93.20)				F2,8720=5.62, P=0.00361
Median (interquartile range)		0.62 (0.40—0.81)	0.57 (0.37—0.77)	0.57 (0.37—0.78)
Range		0.00—1.00	0.00—1.00	0.00—1.00

N is the number of non-missing value. ¹Kruskal-Wallis. ²Pearson. ³Wilcoxon.

3.5 Histogram of MOUD days supplied

3.5.1 Before delivery up to 90 days (Method 1)

3.5.2 Before delivery up to 90 days (Method 2)

3.5.3 Before delivery up to 90 days (Method 3)

3.5.4 After delivery up to 41 days (Method 1)

3.5.5 After delivery up to 41 days (Method 3)

3.5.6 After delivery up to 41 days (Method 3)

3.5.7 Entire exposure (Method 1)

3.5.8 Entire exposure (Method 2)

3.5.9 Entire exposure (Method 3)

Survival Analysis

3.6 Kaplan Meier Plot

Call: survfit(formula = Surv(days.to.event, outcome.bin) ~ 1, data = moud)

        n events median 0.95LCL 0.95UCL
[1,] 9359    147     NA      NA      NA

   Min. 1st Qu.  Median    Mean 3rd Qu.    Max. 
    2.0    92.5   184.5   176.2   258.8   323.0 

time	probability
2	0.9998932
7	0.9997863
8	0.9995726
10	0.9994658
17	0.9993589
18	0.9992521
19	0.9991452
27	0.9990384
32	0.9989315
34	0.9988247
35	0.9986110
38	0.9985041
41	0.9983973
42	0.9982904
43	0.9981836
45	0.9979699
47	0.9978630
52	0.9976493
59	0.9974356
60	0.9973288
61	0.9972219
63	0.9971151
65	0.9970082
66	0.9969014
69	0.9967945
70	0.9966877
72	0.9965808
75	0.9964740
77	0.9963671
87	0.9962603
91	0.9961534
93	0.9960466
95	0.9959397
97	0.9958329
101	0.9956192
110	0.9955123
111	0.9954055
112	0.9952986
118	0.9950849
120	0.9949781
121	0.9948712
125	0.9947644
128	0.9946575
131	0.9945507
138	0.9943370
140	0.9942302
144	0.9941233
147	0.9940165
151	0.9938028
153	0.9936959
156	0.9934822
166	0.9933754
169	0.9932685
171	0.9931617
173	0.9930548
175	0.9929480
177	0.9928411
178	0.9927343
180	0.9926274
181	0.9925206
182	0.9924137
184	0.9923069
185	0.9922000
188	0.9919863
193	0.9918795
199	0.9917726
204	0.9916658
208	0.9915589
211	0.9914521
213	0.9912384
214	0.9911315
215	0.9909178
216	0.9908110
217	0.9905973
220	0.9904904
222	0.9903836
223	0.9902767
228	0.9900630
229	0.9899562
233	0.9898493
235	0.9897425
236	0.9896356
239	0.9895288
240	0.9893151
242	0.9892082
244	0.9891014
245	0.9889946
246	0.9887809
247	0.9886740
250	0.9885672
253	0.9884603
254	0.9883535
258	0.9882466
261	0.9880329
262	0.9879261
263	0.9878192
265	0.9877124
267	0.9876055
268	0.9874987
270	0.9872850
271	0.9871781
272	0.9870713
274	0.9868576
275	0.9867507
279	0.9866439
281	0.9865370
287	0.9863233
289	0.9862165
290	0.9861096
295	0.9860028
296	0.9858959
298	0.9856822
300	0.9855754
301	0.9854685
302	0.9853617
304	0.9852548
305	0.9851480
308	0.9849343
310	0.9847206
313	0.9846137
316	0.9845069
319	0.9844000
321	0.9842932
323	0.9842932

3.7 Time to event for overdose and death

deathod$days.to.event

n	missing	distinct	Info	Mean	pMedian	Gmd	.05	.10	.25	.50	.75	.90	.95
147	0	123	1	176.5	177	108.4	21.4	41.6	94.0	188.0	259.5	296.8	307.1

lowest : 2 7 8 10 17 , highest: 310 313 316 319 321 death$days.to.event

n	missing	distinct	Info	Mean	pMedian	Gmd	.05	.10	.25	.50	.75	.90	.95
38	0	37	1	153	154	111.1	18.7	34.1	59.5	163.5	239.0	276.2	282.3

lowest : 2 17 19 32 35 , highest: 275 279 281 290 308 od$days.to.event

n	missing	distinct	Info	Mean	pMedian	Gmd	.05	.10	.25	.50	.75	.90	.95
109	0	98	1	184.7	185.5	106.5	29.8	44.6	111.0	208.0	262.0	300.2	309.2

lowest : 7 8 10 18 27 , highest: 310 313 316 319 321

4 Multivariable Cox PH model

4.1 Linear continuous terms

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
Year of delivery	2016	2018	2	0.35980	0.08085	0.20130	0.51830
Hazard Ratio	2016	2018	2	1.43300		1.22300	1.67900
Total days supplied MOUD (method 3)	1	31	30	-0.15680	0.06034	-0.27510	-0.03854
Hazard Ratio	1	31	30	0.85490		0.75950	0.96220
Age at delivery	27	31	4	-0.06338	0.07260	-0.20570	0.07892
Hazard Ratio	27	31	4	0.93860		0.81410	1.08200
Number of Gestation weeks	39	37	-2	0.13260	0.06225	0.01056	0.25460
Hazard Ratio	39	37	-2	1.14200		1.01100	1.29000
Route of delivery --- Cesarean:Vaginal	2	1		-0.04018	0.17820	-0.38950	0.30920
Hazard Ratio	2	1		0.96060		0.67740	1.36200
Combined pain --- Yes:No	1	2		-0.16570	0.18730	-0.53280	0.20130
Hazard Ratio	1	2		0.84730		0.58700	1.22300
Alcohol or other substance use --- Yes:No	1	2		0.24720	0.17170	-0.08941	0.58380
Hazard Ratio	1	2		1.28000		0.91450	1.79300
Benzodiazepine or anticonvulsant use --- Yes:No	1	2		0.31570	0.21330	-0.10250	0.73380
Hazard Ratio	1	2		1.37100		0.90260	2.08300
Anxiety and depression combined --- Yes:No	1	2		0.59240	0.18170	0.23620	0.94860
Hazard Ratio	1	2		1.80800		1.26600	2.58200
Maternal morbidity --- Yes:No	1	2		-0.04326	0.35260	-0.73440	0.64790
Hazard Ratio	1	2		0.95770		0.47980	1.91200

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
Year of delivery	19.78	1	<0.0001
Total days supplied MOUD (method 3)	6.75	1	0.0094
Age at delivery	0.76	1	0.3822
Route of delivery	0.05	1	0.8217
Number of Gestation weeks	4.54	1	0.0331
Combined pain	0.78	1	0.3762
Alcohol or other substance use	2.07	1	0.1499
Benzodiazepine or anticonvulsant use	2.19	1	0.1387
Anxiety and depression combined	10.61	1	0.0011
Maternal morbidity	0.02	1	0.9023
TOTAL	66.73	10	<0.0001

4.1.1 Univariable HR

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
Total days supplied MOUD (method 3)	1	31	30	-0.1863	0.06093	-0.3057	-0.06684
Hazard Ratio	1	31	30	0.8301		0.7366	0.93530

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
Total days supplied MOUD (method 3)	9.34	1	0.0022
TOTAL	9.34	1	0.0022

4.2 With splines

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
Year of delivery	2016	2018	2	0.43710	0.09102	0.258700	0.61550
Hazard Ratio	2016	2018	2	1.54800		1.295000	1.85100
Total days supplied MOUD (method 3)	1	31	30	-0.15860	0.05974	-0.275700	-0.04149
Hazard Ratio	1	31	30	0.85340		0.759100	0.95940
Age at delivery	27	31	4	-0.06639	0.07246	-0.208400	0.07563
Hazard Ratio	27	31	4	0.93580		0.811900	1.07900
Number of Gestation weeks	39	37	-2	0.13060	0.06274	0.007666	0.25360
Hazard Ratio	39	37	-2	1.14000		1.008000	1.28900
Route of delivery --- Cesarean:Vaginal	2	1		-0.03955	0.17820	-0.388700	0.30960
Hazard Ratio	2	1		0.96120		0.677900	1.36300
Combined pain --- Yes:No	1	2		-0.17470	0.18800	-0.543100	0.19380
Hazard Ratio	1	2		0.83970		0.580900	1.21400
Alcohol or other substance use --- Yes:No	1	2		0.25740	0.17290	-0.081520	0.59640
Hazard Ratio	1	2		1.29400		0.921700	1.81600
Benzodiazepine or anticonvulsant use --- Yes:No	1	2		0.33490	0.21650	-0.089320	0.75920
Hazard Ratio	1	2		1.39800		0.914600	2.13700
Anxiety and depression combined --- Yes:No	1	2		0.59050	0.18180	0.234100	0.94680
Hazard Ratio	1	2		1.80500		1.264000	2.57800
Maternal morbidity --- Yes:No	1	2		-0.04746	0.35180	-0.737000	0.64210
Hazard Ratio	1	2		0.95360		0.478500	1.90000

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
Year of delivery	28.41	2	<0.0001
Nonlinear	1.65	1	0.1984
Total days supplied MOUD (method 3)	7.04	1	0.0079
Age at delivery	0.84	1	0.3591
Route of delivery	0.05	1	0.8244
Number of Gestation weeks	4.34	1	0.0372
Combined pain	0.86	1	0.3528
Alcohol or other substance use	2.22	1	0.1365
Benzodiazepine or anticonvulsant use	2.40	1	0.1214
Anxiety and depression combined	10.53	1	0.0012
Maternal morbidity	0.02	1	0.8926
TOTAL	77.61	11	<0.0001

4.3 Linear model (only buprenorphine)

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
Year of delivery	2016	2018	2	0.36210	0.08162	0.20220	0.52210
Hazard Ratio	2016	2018	2	1.43600		1.22400	1.68600
Total days supplied buprenorphine	1	31	30	-0.19660	0.06203	-0.31820	-0.07508
Hazard Ratio	1	31	30	0.82150		0.72740	0.92770
Age at delivery	27	31	4	-0.05486	0.07259	-0.19710	0.08741
Hazard Ratio	27	31	4	0.94660		0.82110	1.09100
Number of Gestation weeks	39	37	-2	0.13410	0.06190	0.01277	0.25540
Hazard Ratio	39	37	-2	1.14400		1.01300	1.29100
Route of delivery --- Cesarean:Vaginal	2	1		-0.08087	0.18020	-0.43410	0.27240
Hazard Ratio	2	1		0.92230		0.64780	1.31300
Combined pain --- Yes:No	1	2		-0.16840	0.18780	-0.53650	0.19960
Hazard Ratio	1	2		0.84500		0.58480	1.22100
Alcohol or other substance use --- Yes:No	1	2		0.30260	0.17270	-0.03579	0.64100
Hazard Ratio	1	2		1.35300		0.96480	1.89800
Benzodiazepine or anticonvulsant use --- Yes:No	1	2		0.32320	0.21400	-0.09621	0.74250
Hazard Ratio	1	2		1.38100		0.90830	2.10100
Anxiety and depression combined --- Yes:No	1	2		0.60400	0.18240	0.24640	0.96150
Hazard Ratio	1	2		1.82900		1.27900	2.61600
Maternal morbidity --- Yes:No	1	2		-0.04485	0.35360	-0.73790	0.64820
Hazard Ratio	1	2		0.95610		0.47810	1.91200

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
Year of delivery	19.65	1	<0.0001
Total days supplied buprenorphine	10.05	1	0.0015
Age at delivery	0.57	1	0.4494
Route of delivery	0.20	1	0.6538
Number of Gestation weeks	4.70	1	0.0301
Combined pain	0.80	1	0.3698
Alcohol or other substance use	3.07	1	0.0795
Benzodiazepine or anticonvulsant use	2.28	1	0.1306
Anxiety and depression combined	10.94	1	0.0009
Maternal morbidity	0.02	1	0.8990
TOTAL	70.46	10	<0.0001

4.3.1 Univariate

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
Total days supplied buprenorphine	1	31	30	-0.2250	0.06256	-0.3477	-0.1024
Hazard Ratio	1	31	30	0.7985		0.7063	0.9026

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
Total days supplied buprenorphine	12.93	1	0.0003
TOTAL	12.93	1	0.0003

By MOUD timing

5 Survival analysis

5.1 KM Curves

time	probability
2	0.9991790
8	0.9983580
19	0.9975369
32	0.9967159
45	0.9958949
70	0.9950739
97	0.9942529
101	0.9934319
111	0.9926108
125	0.9917898
131	0.9909688
173	0.9901478
177	0.9893268
217	0.9885057
222	0.9876847
240	0.9868637
244	0.9860427
258	0.9852217
261	0.9844007
270	0.9835796
274	0.9827586
287	0.9819376
310	0.9811166
323	0.9811166
27	0.9988290
35	0.9976581
77	0.9964871
87	0.9953162
91	0.9941452
101	0.9929742
118	0.9918033
138	0.9906323
147	0.9894614
166	0.9882904
193	0.9871194
213	0.9859485
215	0.9847775
217	0.9836066
245	0.9824356
270	0.9812646
272	0.9800937
281	0.9789227
295	0.9777518
300	0.9765808
301	0.9754098
319	0.9742389
323	0.9742389
7	0.9998628
8	0.9997255
10	0.9995883
17	0.9994511
18	0.9993138
34	0.9991766
35	0.9990394
38	0.9989022
41	0.9987649
42	0.9986277
43	0.9984905
45	0.9983532
47	0.9982160
52	0.9979415
59	0.9976671
60	0.9975298
61	0.9973926
63	0.9972554
65	0.9971182
66	0.9969809
69	0.9968437
72	0.9967065
75	0.9965692
93	0.9964320
95	0.9962948
110	0.9961575
112	0.9960203
118	0.9958831
120	0.9957458
121	0.9956086
128	0.9954714
138	0.9953342
140	0.9951969
144	0.9950597
151	0.9947852
153	0.9946480
156	0.9943735
169	0.9942363
171	0.9940991
175	0.9939618
178	0.9938246
180	0.9936874
181	0.9935502
182	0.9934129
184	0.9932757
185	0.9931385
188	0.9928640
199	0.9927268
204	0.9925895
208	0.9924523
211	0.9923151
213	0.9921779
214	0.9920406
215	0.9919034
216	0.9917662
220	0.9916289
223	0.9914917
228	0.9912172
229	0.9910800
233	0.9909428
235	0.9908055
236	0.9906683
239	0.9905311
240	0.9903939
242	0.9902566
246	0.9899822
247	0.9898449
250	0.9897077
253	0.9895705
254	0.9894332
261	0.9892960
262	0.9891588
263	0.9890215
265	0.9888843
267	0.9887471
268	0.9886099
271	0.9884726
274	0.9883354
275	0.9881982
279	0.9880609
287	0.9879237
289	0.9877865
290	0.9876492
296	0.9875120
298	0.9872375
302	0.9871003
304	0.9869631
305	0.9868259
308	0.9865514
310	0.9864142
313	0.9862769
316	0.9861397
321	0.9860025
323	0.9860025

5.2 Log-Rank Test

Call:
survdiff(formula = Surv(days.to.event, outcome.bin) ~ moud.both3div, 
    data = moud)

                                   N Observed Expected (O-E)^2/E (O-E)^2/V
moud.both3div=Only pre          1218       23     19.1     0.804     0.924
moud.both3div=Only post          854       22     13.4     5.593     6.152
moud.both3div=Both pre and post 7287      102    114.6     1.377     6.240

 Chisq= 7.8  on 2 degrees of freedom, p= 0.02 

5.3 Multivariable Cox PH model

Linear continuous terms (timing + days)

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
Total days supplied MOUD (method 3)	1	31	30	-0.11910	0.09134	-0.298100	0.05989
Hazard Ratio	1	31	30	0.88770		0.742200	1.06200
Year of delivery	2016	2018	2	0.36010	0.07985	0.203600	0.51660
Hazard Ratio	2016	2018	2	1.43300		1.226000	1.67600
Age at delivery	27	31	4	-0.06560	0.07251	-0.207700	0.07651
Hazard Ratio	27	31	4	0.93650		0.812400	1.08000
Number of Gestation weeks	39	37	-2	0.12790	0.06164	0.007131	0.24880
Hazard Ratio	39	37	-2	1.13600		1.007000	1.28200
MOUD receipt timing --- Only pre:Both pre and post	3	1		0.03064	0.30440	-0.566100	0.62730
Hazard Ratio	3	1		1.03100		0.567800	1.87300
MOUD receipt timing --- Only post:Both pre and post	3	2		0.25940	0.32340	-0.374400	0.89320
Hazard Ratio	3	2		1.29600		0.687700	2.44300
Route of delivery --- Cesarean:Vaginal	2	1		-0.04128	0.17840	-0.390900	0.30830
Hazard Ratio	2	1		0.95960		0.676500	1.36100
Combined pain --- No:Yes	2	1		0.16060	0.18730	-0.206500	0.52770
Hazard Ratio	2	1		1.17400		0.813400	1.69500
Alcohol or other substance use --- Yes:No	1	2		0.25370	0.17170	-0.082740	0.59020
Hazard Ratio	1	2		1.28900		0.920600	1.80400
Benzodiazepine or anticonvulsant use --- Yes:No	1	2		0.31840	0.21320	-0.099480	0.73620
Hazard Ratio	1	2		1.37500		0.905300	2.08800
Anxiety and depression combined --- Yes:No	1	2		0.58820	0.18080	0.233800	0.94250
Hazard Ratio	1	2		1.80100		1.263000	2.56700
Maternal morbidity --- Yes:No	1	2		-0.04487	0.35240	-0.735500	0.64580
Hazard Ratio	1	2		0.95610		0.479300	1.90700

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
MOUD receipt timing	0.82	2	0.6647
Total days supplied MOUD (method 3)	1.70	1	0.1919
Year of delivery	20.31	1	<0.0001
Age at delivery	0.82	1	0.3651
Route of delivery	0.05	1	0.8171
Number of Gestation weeks	4.32	1	0.0377
Combined pain	0.73	1	0.3913
Alcohol or other substance use	2.19	1	0.1392
Benzodiazepine or anticonvulsant use	2.23	1	0.1350
Anxiety and depression combined	10.57	1	0.0011
Maternal morbidity	0.02	1	0.8986
TOTAL	69.87	12	<0.0001

Timing only

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
Year of delivery	2016	2018	2	0.36170	0.07929	0.20630	0.51710
Hazard Ratio	2016	2018	2	1.43600		1.22900	1.67700
Age at delivery	27	31	4	-0.07190	0.07297	-0.21490	0.07111
Hazard Ratio	27	31	4	0.93060		0.80660	1.07400
Number of Gestation weeks	39	37	-2	0.13180	0.06125	0.01175	0.25180
Hazard Ratio	39	37	-2	1.14100		1.01200	1.28600
MOUD receipt timing --- Only pre:Both pre and post	3	1		0.26730	0.23070	-0.18480	0.71940
Hazard Ratio	3	1		1.30600		0.83130	2.05300
MOUD receipt timing --- Only post:Both pre and post	3	2		0.55190	0.23520	0.09101	1.01300
Hazard Ratio	3	2		1.73700		1.09500	2.75300
Route of delivery --- Cesarean:Vaginal	2	1		-0.04978	0.17780	-0.39830	0.29870
Hazard Ratio	2	1		0.95140		0.67150	1.34800
Combined pain --- No:Yes	2	1		0.16080	0.18740	-0.20640	0.52800
Hazard Ratio	2	1		1.17400		0.81350	1.69600
Alcohol or other substance use --- Yes:No	1	2		0.27220	0.17180	-0.06451	0.60880
Hazard Ratio	1	2		1.31300		0.93750	1.83800
Benzodiazepine or anticonvulsant use --- Yes:No	1	2		0.31880	0.21320	-0.09906	0.73660
Hazard Ratio	1	2		1.37500		0.90570	2.08900
Anxiety and depression combined --- Yes:No	1	2		0.58640	0.18050	0.23260	0.94010
Hazard Ratio	1	2		1.79700		1.26200	2.56000
Maternal morbidity --- Yes:No	1	2		-0.04958	0.35220	-0.73990	0.64070
Hazard Ratio	1	2		0.95160		0.47720	1.89800

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
MOUD receipt timing	6.05	2	0.0485
Year of delivery	20.79	1	<0.0001
Age at delivery	0.97	1	0.3239
Route of delivery	0.08	1	0.7796
Number of Gestation weeks	4.64	1	0.0312
Combined pain	0.74	1	0.3909
Alcohol or other substance use	2.51	1	0.1129
Benzodiazepine or anticonvulsant use	2.24	1	0.1345
Anxiety and depression combined	10.55	1	0.0012
Maternal morbidity	0.02	1	0.8880
TOTAL	69.29	11	<0.0001

Linear continuous terms (timing + days BUP)

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
Total days supplied buprenorphine	1	31	30	-0.151000	0.09363	-0.33450	0.032490
Hazard Ratio	1	31	30	0.859800		0.71570	1.033000
Year of delivery	2014	2018	4	0.725300	0.15990	0.41190	1.039000
Hazard Ratio	2014	2018	4	2.065000		1.51000	2.825000
Age at delivery	25	35	10	-0.144400	0.18120	-0.49970	0.210800
Hazard Ratio	25	35	10	0.865500		0.60670	1.235000
Number of Gestation weeks	37	39	2	-0.126900	0.06091	-0.24630	-0.007551
Hazard Ratio	37	39	2	0.880800		0.78170	0.992500
MOUD receipt timing --- Only pre:Both pre and post	3	1		0.003667	0.30750	-0.59890	0.606300
Hazard Ratio	3	1		1.004000		0.54940	1.834000
MOUD receipt timing --- Only post:Both pre and post	3	2		0.360500	0.32610	-0.27870	0.999600
Hazard Ratio	3	2		1.434000		0.75680	2.717000
Route of delivery --- Cesarean:Vaginal	2	1		-0.082460	0.18020	-0.43570	0.270800
Hazard Ratio	2	1		0.920900		0.64680	1.311000
Combined pain --- No:Yes	2	1		0.158900	0.18800	-0.20950	0.527300
Hazard Ratio	2	1		1.172000		0.81100	1.694000
Alcohol or other substance use --- Yes:No	1	2		0.316800	0.17250	-0.02136	0.655000
Hazard Ratio	1	2		1.373000		0.97890	1.925000
Benzodiazepine or anticonvulsant use --- Yes:No	1	2		0.326200	0.21380	-0.09290	0.745200
Hazard Ratio	1	2		1.386000		0.91130	2.107000
Anxiety and depression combined --- Yes:No	1	2		0.601100	0.18180	0.24470	0.957500
Hazard Ratio	1	2		1.824000		1.27700	2.605000
Maternal morbidity --- Yes:No	1	2		-0.048310	0.35330	-0.74070	0.644100
Hazard Ratio	1	2		0.952800		0.47680	1.904000

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
MOUD receipt timing	1.77	2	0.4132
Total days supplied buprenorphine	2.60	1	0.1066
Year of delivery	20.55	1	<0.0001
Age at delivery	0.64	1	0.4252
Route of delivery	0.21	1	0.6475
Number of Gestation weeks	4.35	1	0.0370
Combined pain	0.71	1	0.3979
Alcohol or other substance use	3.38	1	0.0662
Benzodiazepine or anticonvulsant use	2.33	1	0.1268
Anxiety and depression combined	10.91	1	0.0010
Maternal morbidity	0.02	1	0.8911
TOTAL	76.10	12	<0.0001

Timing only BUP

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
Year of delivery	2014	2018	4	0.73050	0.15850	0.419900	1.04100
Hazard Ratio	2014	2018	4	2.07600		1.522000	2.83300
Age at delivery	25	35	10	-0.16380	0.18250	-0.521400	0.19380
Hazard Ratio	25	35	10	0.84890		0.593700	1.21400
Number of Gestation weeks	37	39	2	-0.13200	0.06041	-0.250400	-0.01357
Hazard Ratio	37	39	2	0.87640		0.778500	0.98650
MOUD receipt timing --- Only pre:Both pre and post	3	1		0.30200	0.23150	-0.151700	0.75560
Hazard Ratio	3	1		1.35300		0.859300	2.12900
MOUD receipt timing --- Only post:Both pre and post	3	2		0.72830	0.23700	0.263700	1.19300
Hazard Ratio	3	2		2.07200		1.302000	3.29600
Route of delivery --- Cesarean:Vaginal	2	1		-0.09451	0.17980	-0.446900	0.25790
Hazard Ratio	2	1		0.90980		0.639600	1.29400
Combined pain --- No:Yes	2	1		0.15970	0.18810	-0.208900	0.52830
Hazard Ratio	2	1		1.17300		0.811500	1.69600
Alcohol or other substance use --- Yes:No	1	2		0.34090	0.17320	0.001428	0.68030
Hazard Ratio	1	2		1.40600		1.001000	1.97500
Benzodiazepine or anticonvulsant use --- Yes:No	1	2		0.32740	0.21380	-0.091680	0.74650
Hazard Ratio	1	2		1.38700		0.912400	2.11000
Anxiety and depression combined --- Yes:No	1	2		0.59910	0.18150	0.243300	0.95490
Hazard Ratio	1	2		1.82000		1.275000	2.59800
Maternal morbidity --- Yes:No	1	2		-0.05515	0.35300	-0.747100	0.63680
Hazard Ratio	1	2		0.94630		0.473700	1.89000

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
MOUD receipt timing	9.98	2	0.0068
Year of delivery	21.22	1	<0.0001
Age at delivery	0.81	1	0.3690
Route of delivery	0.28	1	0.5994
Number of Gestation weeks	4.78	1	0.0287
Combined pain	0.72	1	0.3958
Alcohol or other substance use	3.88	1	0.0489
Benzodiazepine or anticonvulsant use	2.35	1	0.1254
Anxiety and depression combined	10.88	1	0.0010
Maternal morbidity	0.02	1	0.8757
TOTAL	75.51	11	<0.0001

6 Sensitivity analysis 2007-2018

6.1 Descriptive Statistics

• There are 5728 pregnancies in 5049 unique individuals

  	N	Overall
  		(N=7362)
  Year of delivery	7362 (100.00)
  Median (interquartile range)		2015 (2013—2017)
  Range		2007—2018
  Age at delivery	7362 (100.00)
  Median (interquartile range)		27 (24—30)
  Range		17—44
  Number of Gestation weeks	7362 (100.00)
  Median (interquartile range)		39 (37—39)
  Range		21—42
  Race	7338 (99.67)
  American Indian or Alaska Native		19/7338 (0.26)
  Asian or Pacific Islander		9/7338 (0.12)
  Black of African American		165/7338 (2.25)
  Other or Unknown		48/7338 (0.65)
  White		7097/7338 (96.72)
  Hispanic : Not Hispanic	7331 (99.58)	7274/7331 (99.22)
  Race/Ethnicity combined	7338 (99.67)
  Hispanic		57/7338 (0.78)
  Non-Hispanic Asian		8/7338 (0.11)
  Non-Hispanic Black		164/7338 (2.23)
  Non-Hispanic Other		51/7338 (0.70)
  Non-Hispanic White		7058/7338 (96.18)
  Route of delivery : Vaginal	7338 (99.67)	4816/7338 (65.63)
  Number of previous pregnancies	7178 (97.50)
  Median (interquartile range)		2 (1—3)
  Range		0—23
  Final outcome	7362 (100.00)
  Death		27/7362 (0.37)
  Overdose		64/7362 (0.87)
  Loss of enrollment		1011/7362 (13.73)
  Censored		6260/7362 (85.03)
  Final outcome (w/o all payer data)	7362 (100.00)
  Death		11/7362 (0.15)
  Overdose		59/7362 (0.80)
  Loss of enrollment		1032/7362 (14.02)
  Censored		6260/7362 (85.03)
  Total days supplied MOUD	7362 (100.00)
  Median (interquartile range)		92 (53—120)
  Range		1—132
  Total days supplied MOUD before delivery	7362 (100.00)
  Median (interquartile range)		73 (33—90)
  Range		0—90
  Total days supplied MOUD after delivery	7362 (100.00)
  Median (interquartile range)		29 (7—41)
  Range		0—42
  Total days supplied MOUD (method 2)	7362 (100.00)
  Median (interquartile range)		96 (53—121)
  Range		1—132
  Total days supplied MOUD before delivery (method 2)	7362 (100.00)
  Median (interquartile range)		73 (33—90)
  Range		0—90
  Total days supplied MOUD after delivery (method 2)	7362 (100.00)
  Median (interquartile range)		30 (10—42)
  Range		0—42
  Total days supplied MOUD (method 3)	7362 (100.00)
  Median (interquartile range)		88 (45—110)
  Range		1—132
  Total days supplied MOUD before delivery (method 3)	7362 (100.00)
  Median (interquartile range)		61 (29—77)
  Range		0—90
  Total days supplied MOUD after delivery (method 3)	7362 (100.00)
  Median (interquartile range)		29 (12—40)
  Range		0—42
  Avg dose pre-delivery (mg)	7303 (99.20)
  Median (interquartile range)		14.30 (8.00—16.00)
  Range		0.00—50.00
  Avg dose post-delivery (mg)	7303 (99.20)
  Median (interquartile range)		9.65 (3.94—16.00)
  Range		0.00—53.57
  Avg dose exposure (mg)	7303 (99.20)
  Median (interquartile range)		14.23 (9.85—16.00)
  Range		0.00—53.57
  Total days buprenorphine before delivery (method 3)	7255 (98.55)
  Median (interquartile range)		62.00 (30.00—77.00)
  Range		0.00—90.00
  Total days buprenorphine after delivery (method 3)	7255 (98.55)
  Median (interquartile range)		29.00 (12.00—40.00)
  Range		0.00—42.00
  Total days supplied buprenorphine	7255 (98.55)
  Median (interquartile range)		88.00 (46.00—110.00)
  Range		1.00—132.00
  Avg dose BUP pre-delivery (mg)	7255 (98.55)
  Median (interquartile range)		14.25 (8.00—16.00)
  Range		0.00—40.00
  Avg dose BUP post-delivery (mg)	7255 (98.55)
  Median (interquartile range)		9.60 (4.00—16.00)
  Range		0.00—42.67
  Avg dose BUP exposure (mg)	7255 (98.55)
  Median (interquartile range)		14.17 (9.75—16.00)
  Range		0.00—42.67
  Combined pain : Yes	7362 (100.00)	5765/7362 (78.31)
  Schizophrenia or personality disorder : Yes	7362 (100.00)	501/7362 (6.81)
  Alcohol or other substance use : Yes	7362 (100.00)	3303/7362 (44.87)
  Benzodiazepine or anticonvulsant use : Yes	7362 (100.00)	1101/7362 (14.96)
  Maternal morbidity : Yes	7362 (100.00)	573/7362 (7.78)
  Anxiety and depression combined : Yes	7362 (100.00)	3012/7362 (40.91)
  Back pain : Yes	7362 (100.00)	3039/7362 (41.28)
  Depression : Yes	7362 (100.00)	2605/7362 (35.38)
  Bipolar disorder : Yes	7362 (100.00)	690/7362 (9.37)
  Other substance use : Yes	7362 (100.00)	3148/7362 (42.76)
  Tobacco use : Yes	7362 (100.00)	5039/7362 (68.45)
  Med NSAIDS : Yes	7362 (100.00)	4405/7362 (59.83)
  Schizophrenia psychotic disorders : Yes	7362 (100.00)	376/7362 (5.11)
  Anxiety : Yes	7362 (100.00)	1150/7362 (15.62)
  Med benzodiazepine use : Yes	7362 (100.00)	748/7362 (10.16)
  Maternal morbidity : Yes	7362 (100.00)	573/7362 (7.78)
  Dental pain : Yes	7362 (100.00)	273/7362 (3.71)
  Alcohol use disorder : Yes	7362 (100.00)	459/7362 (6.23)
  Med anticonvulsant use : Yes	7362 (100.00)	426/7362 (5.79)
  Med muscle relaxant use : Yes	7362 (100.00)	350/7362 (4.75)
  Personality disorder : Yes	7362 (100.00)	208/7362 (2.83)
  Fibromyalgia : Yes	7362 (100.00)	371/7362 (5.04)
  CDC SVI overall percentile ranking of all 4 themes	6811 (92.52)
  Median (interquartile range)		0.57 (0.37—0.78)
  Range		0.00—1.00

  N is the number of non-missing value. ¹Kruskal-Wallis. ²Pearson. ³Wilcoxon.

6.1.1 Time to event for overdose and death

deathod18$days.to.event

n	missing	distinct	Info	Mean	pMedian	Gmd	.05	.10	.25	.50	.75	.90	.95
91	0	84	1	181.4	182	107.5	23.0	43.0	111.5	188.0	267.5	296.0	306.0

lowest : 2 7 8 18 19 , highest: 304 308 310 316 319 death18$days.to.event

n	missing	distinct	Info	Mean	pMedian	Gmd	.05	.10	.25	.50	.75	.90	.95
27	0	26	1	158.9	159.5	116.6	23.8	36.8	56.5	171.0	264.0	279.8	287.3

lowest : 2 19 35 38 45 , highest: 275 279 281 290 308 od18$days.to.event

n	missing	distinct	Info	Mean	pMedian	Gmd	.05	.10	.25	.50	.75	.90	.95
64	0	61	1	190.9	195	102.7	29.25	51.80	123.75	213.00	268.50	300.10	309.10

lowest : 7 8 18 27 42 , highest: 302 304 310 316 319

Survival Analysis

6.2 Kaplan Meier Plot

Call: survfit(formula = Surv(days.to.event, outcome.bin) ~ 1, data = moud18)

        n events median 0.95LCL 0.95UCL
[1,] 7362     91     NA      NA      NA

   Min. 1st Qu.  Median    Mean 3rd Qu.    Max. 
    2.0   111.0   184.0   181.1   268.0   323.0 

time	probability
2	0.9998642
7	0.9997283
8	0.9995925
18	0.9994567
19	0.9993208
27	0.9991850
35	0.9990492
38	0.9989133
42	0.9987775
43	0.9986417
45	0.9985058
47	0.9983700
52	0.9980983
61	0.9979625
63	0.9978267
66	0.9976908
69	0.9975550
72	0.9974192
91	0.9972833
97	0.9971475
110	0.9970117
111	0.9968758
112	0.9967400
118	0.9966042
120	0.9964684
125	0.9963325
128	0.9961967
131	0.9960609
138	0.9957892
140	0.9956534
144	0.9955175
147	0.9953817
156	0.9952459
166	0.9951100
169	0.9949742
171	0.9948384
175	0.9947025
177	0.9945667
178	0.9944309
180	0.9942950
181	0.9941592
182	0.9940234
184	0.9938875
188	0.9937517
199	0.9936159
208	0.9934800
213	0.9932084
215	0.9930725
217	0.9928009
220	0.9926650
222	0.9925292
223	0.9923934
228	0.9922575
229	0.9921217
235	0.9919859
239	0.9918500
240	0.9915784
244	0.9914425
246	0.9913067
258	0.9911709
261	0.9910350
265	0.9908992
267	0.9907634
268	0.9906275
270	0.9903559
271	0.9902200
272	0.9900842
274	0.9899484
275	0.9898126
279	0.9896767
281	0.9895409
287	0.9894051
289	0.9892692
290	0.9891334
295	0.9889976
296	0.9888617
298	0.9887259
301	0.9885901
302	0.9884542
304	0.9883184
308	0.9881826
310	0.9879109
316	0.9877751
319	0.9876392
323	0.9876392

Multivariable Cox PH model

6.2.1 Linear continuous terms

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
Year of delivery	2016	2018	2	0.29370	0.11910	0.06013	0.52720
Hazard Ratio	2016	2018	2	1.34100		1.06200	1.69400
Total days supplied MOUD (method 3)	1	31	30	-0.21430	0.07791	-0.36700	-0.06157
Hazard Ratio	1	31	30	0.80710		0.69280	0.94030
Age at delivery	27	31	4	-0.03848	0.09597	-0.22660	0.14960
Hazard Ratio	27	31	4	0.96220		0.79720	1.16100
Number of Gestation weeks	39	37	-2	0.16990	0.07551	0.02191	0.31790
Hazard Ratio	39	37	-2	1.18500		1.02200	1.37400
Route of delivery --- Cesarean:Vaginal	2	1		0.15100	0.22170	-0.28350	0.58560
Hazard Ratio	2	1		1.16300		0.75310	1.79600
Combined pain --- No:Yes	2	1		0.17670	0.25090	-0.31520	0.66850
Hazard Ratio	2	1		1.19300		0.72960	1.95100
Alcohol or other substance use --- Yes:No	1	2		-0.06176	0.21700	-0.48710	0.36360
Hazard Ratio	1	2		0.94010		0.61440	1.43800
Benzodiazepine or anticonvulsant use --- Yes:No	1	2		0.28060	0.26720	-0.24320	0.80440
Hazard Ratio	1	2		1.32400		0.78410	2.23500
Anxiety and depression combined --- Yes:No	1	2		0.59970	0.22430	0.16000	1.03900
Hazard Ratio	1	2		1.82200		1.17400	2.82800
Maternal morbidity --- Yes:No	1	2		-0.11350	0.42620	-0.94880	0.72180
Hazard Ratio	1	2		0.89270		0.38720	2.05800

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
Year of delivery	6.06	1	0.0138
Total days supplied MOUD (method 3)	7.56	1	0.0060
Age at delivery	0.16	1	0.6882
Route of delivery	0.46	1	0.4959
Number of Gestation weeks	5.07	1	0.0243
Combined pain	0.50	1	0.4814
Alcohol or other substance use	0.08	1	0.7758
Benzodiazepine or anticonvulsant use	1.10	1	0.2932
Anxiety and depression combined	7.14	1	0.0075
Maternal morbidity	0.07	1	0.7900
TOTAL	43.96	10	<0.0001

6.2.2 Univariable HR

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
Total days supplied MOUD (method 3)	1	31	30	-0.2358	0.07787	-0.3884	-0.08315
Hazard Ratio	1	31	30	0.7900		0.6781	0.92020

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
Total days supplied MOUD (method 3)	9.16	1	0.0025
TOTAL	9.16	1	0.0025

7 Sensitivity analysis shift-forward

	N	Overall
		(N=9359)
Total days supplied MOUD (method 3)	9359 (100.00)
Median (interquartile range)		88 (43—111)
Range		1—132
MOUD days exposure shifted approach	9359 (100.00)
Median (interquartile range)		91 (47—115)
Range		1—132

N is the number of non-missing value. ¹Kruskal-Wallis. ²Pearson. ³Wilcoxon.

7.1 Survival Analysis

Multivariable Cox PH model

Linear continuous terms

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
Year of delivery	2016	2018	2	0.36090	0.08074	0.20270	0.51920
Hazard Ratio	2016	2018	2	1.43500		1.22500	1.68100
MOUD days exposure shifted approach	1	31	30	-0.14760	0.05955	-0.26430	-0.03087
Hazard Ratio	1	31	30	0.86280		0.76770	0.96960
Age at delivery	27	31	4	-0.06354	0.07266	-0.20600	0.07888
Hazard Ratio	27	31	4	0.93840		0.81390	1.08200
Number of Gestation weeks	39	37	-2	0.13320	0.06207	0.01150	0.25480
Hazard Ratio	39	37	-2	1.14200		1.01200	1.29000
Route of delivery --- Cesarean:Vaginal	2	1		-0.04131	0.17820	-0.39060	0.30800
Hazard Ratio	2	1		0.95950		0.67670	1.36100
Combined pain --- No:Yes	2	1		0.16480	0.18730	-0.20220	0.53180
Hazard Ratio	2	1		1.17900		0.81690	1.70200
Alcohol or other substance use --- Yes:No	1	2		0.25190	0.17180	-0.08486	0.58870
Hazard Ratio	1	2		1.28600		0.91860	1.80200
Benzodiazepine or anticonvulsant use --- Yes:No	1	2		0.31470	0.21340	-0.10350	0.73300
Hazard Ratio	1	2		1.37000		0.90160	2.08100
Anxiety and depression combined --- Yes:No	1	2		0.59350	0.18170	0.23740	0.94970
Hazard Ratio	1	2		1.81000		1.26800	2.58500
Maternal morbidity --- Yes:No	1	2		-0.04384	0.35250	-0.73480	0.64710
Hazard Ratio	1	2		0.95710		0.47960	1.91000

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
Year of delivery	19.95	1	<0.0001
MOUD days exposure shifted approach	6.14	1	0.0132
Age at delivery	0.77	1	0.3814
Route of delivery	0.05	1	0.8168
Number of Gestation weeks	4.61	1	0.0318
Combined pain	0.77	1	0.3789
Alcohol or other substance use	2.15	1	0.1425
Benzodiazepine or anticonvulsant use	2.18	1	0.1400
Anxiety and depression combined	10.65	1	0.0011
Maternal morbidity	0.02	1	0.9010
TOTAL	66.60	10	<0.0001

7.1.1 Univariable HR

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
MOUD days exposure shifted approach	1	31	30	-0.1727	0.06042	-0.2912	-0.05432
Hazard Ratio	1	31	30	0.8413		0.7474	0.94710

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
MOUD days exposure shifted approach	8.17	1	0.0043
TOTAL	8.17	1	0.0043